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P55157 (MTP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Microsomal triglyceride transfer protein large subunit
Gene names
Name:MTTP
Synonyms:MTP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length894 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces. Required for the secretion of plasma lipoproteins that contain apolipoprotein B.

Subunit structure

Heterodimer composed of MTTP and of protein disulfide isomerase (P4HB/PDI) By similarity.

Subcellular location

Endoplasmic reticulum.

Tissue specificity

Liver and small intestine. Also found in ovary, testis and kidney. Ref.6

Induction

Positively regulated by cholesterol and negatively regulated by insulin. Ref.6

Involvement in disease

Abetalipoproteinemia (ABL) [MIM:200100]: An autosomal recessive disorder of lipoprotein metabolism. Affected individuals produce virtually no circulating apolipoprotein B-containing lipoproteins (chylomicrons, VLDL, LDL, lipoprotein(A)). Malabsorption of the antioxidant vitamin E occurs, leading to spinocerebellar and retinal degeneration.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12

Sequence similarities

Contains 1 vitellogenin domain.

Ontologies

Keywords
   Biological processTransport
   Cellular componentEndoplasmic reticulum
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSignal
   LigandLipid-binding
   PTMDisulfide bond
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol homeostasis

Inferred from electronic annotation. Source: Ensembl

lipid metabolic process

Traceable author statement PubMed 1439810. Source: ProtInc

lipoprotein metabolic process

Traceable author statement. Source: Reactome

lipoprotein transport

Inferred from electronic annotation. Source: Ensembl

protein lipidation

Inferred from electronic annotation. Source: Ensembl

response to calcium ion

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

brush border membrane

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum lumen

Traceable author statement. Source: Reactome

membrane-bounded vesicle

Inferred from electronic annotation. Source: Ensembl

microvillus membrane

Inferred from electronic annotation. Source: Ensembl

receptor complex

Inferred from direct assay PubMed 23382219. Source: MGI

rough endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionlipid binding

Inferred from electronic annotation. Source: UniProtKB-KW

lipid transporter activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 894876Microsomal triglyceride transfer protein large subunit
PRO_0000041593

Regions

Domain28 – 659632Vitellogenin

Natural variations

Natural variant951Q → H. Ref.13
Corresponds to variant rs61733139 [ dbSNP | Ensembl ].
VAR_014016
Natural variant981E → D.
Corresponds to variant rs2306986 [ dbSNP | Ensembl ].
VAR_052961
Natural variant1281I → T. Ref.13 Ref.14
Corresponds to variant rs3816873 [ dbSNP | Ensembl ].
VAR_014017
Natural variant1661N → S.
Corresponds to variant rs3792683 [ dbSNP | Ensembl ].
VAR_052962
Natural variant1681V → I Rare polymorphism. Ref.14
Corresponds to variant rs61750974 [ dbSNP | Ensembl ].
VAR_022658
Natural variant2441Q → E. Ref.13
Corresponds to variant rs17599091 [ dbSNP | Ensembl ].
VAR_014018
Natural variant2971H → Q. Ref.10 Ref.13 Ref.14
Corresponds to variant rs2306985 [ dbSNP | Ensembl ].
VAR_010640
Natural variant3541E → Q.
Corresponds to variant rs12933 [ dbSNP | Ensembl ].
VAR_014916
Natural variant3841D → A. Ref.10
Corresponds to variant rs17029215 [ dbSNP | Ensembl ].
VAR_010641
Natural variant5401R → H in ABL; loss of activity. Ref.10 Ref.11
VAR_010642
Natural variant5901S → I in ABL. Ref.11
VAR_010643
Natural variant7461G → E in ABL. Ref.11
VAR_010644
Natural variant7801N → Y in ABL; loss of activity. Ref.12
VAR_014019

Experimental info

Mutagenesis5401R → K: No change of activity. Ref.10
Mutagenesis8781C → S: Loss of activity. Ref.8
Sequence conflict5851F → L in CAA42200. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P55157 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: B20260C136BDAB9F

FASTA89499,351
        10         20         30         40         50         60 
MILLAVLFLC FISSYSASVK GHTTGLSLNN DRLYKLTYST EVLLDRGKGK LQDSVGYRIS 

        70         80         90        100        110        120 
SNVDVALLWR NPDGDDDQLI QITMKDVNVE NVNQQRGEKS IFKGKSPSKI MGKENLEALQ 

       130        140        150        160        170        180 
RPTLLHLIHG KVKEFYSYQN EAVAIENIKR GLASLFQTQL SSGTTNEVDI SGNCKVTYQA 

       190        200        210        220        230        240 
HQDKVIKIKA LDSCKIARSG FTTPNQVLGV SSKATSVTTY KIEDSFVIAV LAEETHNFGL 

       250        260        270        280        290        300 
NFLQTIKGKI VSKQKLELKT TEAGPRLMSG KQAAAIIKAV DSKYTAIPIV GQVFQSHCKG 

       310        320        330        340        350        360 
CPSLSELWRS TRKYLQPDNL SKAEAVRNFL AFIQHLRTAK KEEILQILKM ENKEVLPQLV 

       370        380        390        400        410        420 
DAVTSAQTSD SLEAILDFLD FKSDSSIILQ ERFLYACGFA SHPNEELLRA LISKFKGSIG 

       430        440        450        460        470        480 
SSDIRETVMI ITGTLVRKLC QNEGCKLKAV VEAKKLILGG LEKAEKKEDT RMYLLALKNA 

       490        500        510        520        530        540 
LLPEGIPSLL KYAEAGEGPI SHLATTALQR YDLPFITDEV KKTLNRIYHQ NRKVHEKTVR 

       550        560        570        580        590        600 
TAAAAIILNN NPSYMDVKNI LLSIGELPQE MNKYMLAIVQ DILRFEMPAS KIVRRVLKEM 

       610        620        630        640        650        660 
VAHNYDRFSR SGSSSAYTGY IERSPRSAST YSLDILYSGS GILRRSNLNI FQYIGKAGLH 

       670        680        690        700        710        720 
GSQVVIEAQG LEALIAATPD EGEENLDSYA GMSAILFDVQ LRPVTFFNGY SDLMSKMLSA 

       730        740        750        760        770        780 
SGDPISVVKG LILLIDHSQE LQLQSGLKAN IEVQGGLAID ISGAMEFSLW YRESKTRVKN 

       790        800        810        820        830        840 
RVTVVITTDI TVDSSFVKAG LETSTETEAG LEFISTVQFS QYPFLVCMQM DKDEAPFRQF 

       850        860        870        880        890 
EKKYERLSTG RGYVSQKRKE SVLAGCEFPL HQENSEMCKV VFAPQPDSTS SGWF 

« Hide

References

« Hide 'large scale' references
[1]"Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein."
Shoulders C.C., Brett D.J., Bayliss J.D., Narcisi T.M.E., Jarmuz A., Grantham T.T., Leoni P.R.D., Bhattacharya S., Pease R.J., Cullen P.M., Levi S., Byfield P.G.H., Purkiss P., Scott J.
Hum. Mol. Genet. 2:2109-2116(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Small intestine.
[2]"Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia."
Sharp D., Blinderman L., Combs K.A., Kienzle B., Ricci B., Wager-Smith K., Gil C.M., Turck C.W., Bouma M.-E., Rader D.J., Aggerbeck L.P., Gregg R.E., Gordon D.A., Wetterau J.R.
Nature 365:65-69(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"Human microsomal triglyceride transfer protein large subunit gene structure."
Sharp D., Ricci B., Kienzle B., Lin M.C., Wetterau J.R.
Biochemistry 33:9057-9061(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"Transcriptional regulation of human and hamster microsomal triglyceride transfer protein genes. Cell type-specific expression and response to metabolic regulators."
Hagan D.L., Kienzle B., Jamil H., Hariharan N.
J. Biol. Chem. 269:28737-28744(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
[7]"The abetalipoproteinemia gene is a member of the vitellogenin family and encodes an alpha-helical domain."
Shoulders C.C., Narcisi T.M.E., Read J., Chester S.A., Brett D.J., Scott J., Anderson T.A., Levitt D.G., Banaszak L.J.
Nat. Struct. Biol. 1:285-286(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: SIMILARITY TO VITELLOGENINS.
[8]"Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia."
Narcisi T.M.E., Shoulders C.C., Chester S.A., Read J., Brett D.J., Harrison G.B., Grantham T.T., Fox M.F., Povey S., de Bruin T.W.A., Erkelens D.W., Muller D.P.R., Lloyd J.K., Scott J.
Am. J. Hum. Genet. 57:1298-1310(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF CYS-878.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triglyceride transfer protein that prevents complex formation with protein disulfide isomerase."
Rehberg E.F., Samson-Bouma M.-E., Kienzle B., Blinderman L., Jamil H., Wetterau J.R., Aggerbeck L.P., Gordon D.A.
J. Biol. Chem. 271:29945-29952(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ABL HIS-540, VARIANTS GLN-297 AND ALA-384, MUTAGENESIS OF ARG-540.
[11]"Microsomal triglyceride transfer protein (MTP) gene mutations in Canadian subjects with abetalipoproteinemia."
Wang J., Hegele R.A.
Hum. Mutat. 15:294-295(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ABL HIS-540; ILE-590 AND GLU-746.
[12]"Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia."
Ohashi K., Ishibashi S., Osuga J., Tozawa R., Harada K., Yahagi N., Shionoiri F., Iizuka Y., Tamura Y., Nagai R., Illingworth D.R., Gotoda T., Yamada N.
J. Lipid Res. 41:1199-1204(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ABL TYR-780.
[13]"Variants of the microsomal triglyceride transfer protein gene are associated with plasma cholesterol levels and body mass index."
Ledmyr H., Karpe F., Lundahl B., McKinnon M., Skoglund-Andersson C., Ehrenborg E.
J. Lipid Res. 43:51-58(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HIS-95; THR-128; GLU-244 AND GLN-297.
[14]"Hypobetalipoproteinemia with an apparently recessive inheritance due to a 'de novo' mutation of apolipoprotein B."
Lancellotti S., Di Leo E., Penacchioni J.Y., Balli F., Viola L., Bertolini S., Calandra S., Tarugi P.
Biochim. Biophys. Acta 1688:61-67(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-128; ILE-168 AND GLN-297.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X75500 mRNA. Translation: CAA53217.1.
X59657 mRNA. Translation: CAA42200.1.
X83013 expand/collapse EMBL AC list , X83014, X83015, X83016, X83017, X83018, X83019, X83020, X83021, X83022, X83023, X83024, X83025, X83026, X83027, X83028, X83029, X83030 Genomic DNA. Translation: CAA58142.1.
AK290793 mRNA. Translation: BAF83482.1.
BC125110 mRNA. Translation: AAI25111.1.
BC125111 mRNA. Translation: AAI25112.1.
PIRI38047.
RefSeqNP_000244.2. NM_000253.2.
UniGeneHs.195799.

3D structure databases

ProteinModelPortalP55157.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110641. 1 interaction.
MINTMINT-1537333.
STRING9606.ENSP00000265517.

Chemistry

BindingDBP55157.
ChEMBLCHEMBL2569.
DrugBankDB01094. Hesperetin.

PTM databases

PhosphoSiteP55157.

Polymorphism databases

DMDM1709167.

Proteomic databases

PaxDbP55157.
PRIDEP55157.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265517; ENSP00000265517; ENSG00000138823.
ENST00000457717; ENSP00000400821; ENSG00000138823.
GeneID4547.
KEGGhsa:4547.
UCSCuc003hvc.4. human.

Organism-specific databases

CTD4547.
GeneCardsGC04P100485.
HGNCHGNC:7467. MTTP.
HPAHPA054862.
MIM157147. gene.
200100. phenotype.
neXtProtNX_P55157.
Orphanet14. Abetalipoproteinemia.
426. Familial hypobetalipoproteinemia.
PharmGKBPA164742099.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG272516.
HOGENOMHOG000113688.
HOVERGENHBG006416.
InParanoidP55157.
KOK14463.
PhylomeDBP55157.
TreeFamTF328754.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP55157.
BgeeP55157.
CleanExHS_MTTP.
GenevestigatorP55157.

Family and domain databases

Gene3D1.25.10.20. 1 hit.
2.30.230.10. 1 hit.
InterProIPR015819. Lipid_transp_b-sht_shell.
IPR001747. Lipid_transpt_N.
IPR015816. Vitellinogen_b-sht_N.
IPR011030. Vitellinogen_superhlx.
[Graphical view]
PfamPF01347. Vitellogenin_N. 1 hit.
[Graphical view]
SMARTSM00638. LPD_N. 1 hit.
[Graphical view]
SUPFAMSSF48431. SSF48431. 1 hit.
SSF56968. SSF56968. 1 hit.
PROSITEPS51211. VITELLOGENIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMicrosomal_triglyceride_transfer_protein.
GenomeRNAi4547.
NextBio17529.
PROP55157.
SOURCESearch...

Entry information

Entry nameMTP_HUMAN
AccessionPrimary (citable) accession number: P55157
Secondary accession number(s): A8K428, Q08AM4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: March 19, 2014
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM